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JCR 2016
جستجوی مقالات
شنبه 22 آذر 1404
Iranian Journal of Basic Medical Sciences
، جلد ۲۷، شماره ۲، صفحات ۱۵۷-۱۶۴
عنوان فارسی
چکیده فارسی مقاله
کلیدواژههای فارسی مقاله
عنوان انگلیسی
Targeting GABARAPL1/HIF-2a axis to induce tumor cell apoptosis in nasopharyngeal carcinoma
چکیده انگلیسی مقاله
Objective(s): The primary gene mutations associated with nasopharyngeal carcinoma (NPC) are located within the phosphoinositide 3-kinase-mammalian target of rapamycin signaling pathways, which have inhibitory effects on autophagy. Compounds that target autophagy could potentially be used to treat NPC. However, autophagy-related molecular targets in NPC remain to be elucidated. We aimed to examine levels of autophagy-related genes, including autophagy-related 4B cysteine peptidase (ATG4B) and gamma-aminobutyric acid (GABA) type A receptor-associated protein-like 1 (GABARAPL1), in NPC cells and explored their potential role as novel targets for the treatment of NPC.Materials and Methods: The mRNA and protein expression of autophagy-related genes were detected in several NPC cells. Levels of GABARAPL1 were modified by either overexpression or knockdown, followed by examining downstream targets using RT-qPCR and western blotting. The role of GABARAPL1 in NPC proliferation and apoptosis was examined by flow cytometry. Furthermore, the role of GABARAPL1 was assessed in vivo using a nude mouse xenograft tumor model. The underlying mechanism by which GABARAPL1 regulated nasopharyngeal tumor growth was investigated.Results: Autophagy-related 4B cysteine peptidase (ATG4B), GABARAPL1, and Unc-51-like kinase 1 (ULK1) were significantly down-regulated in multiple NPC cell lines. Overexpression of GABARAPL1 up-regulated the expression of autophagy-related proteins, decreased the level of hypoxia-inducible factor (HIF)-2α, and induced apoptosis in NPC cells. Importantly, overexpression of GABARAPL1 slowed tumor growth. Western blotting showed that autophagy was activated, and HIF-2α was down-regulated in tumor tissues.Conclusion: HIF-2α, as a substrate for autophagic degradation, may play an interesting role during NPC progression.
کلیدواژههای انگلیسی مقاله
ATG4B, Autophagy, GABARAPL1, Hypoxia inducible factor, Nasopharyngeal carcinoma
نویسندگان مقاله
| Xiaopeng Huang
Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province 570311, People’s Republic of China
| Liya Zhou
Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province 570311, People’s Republic of China
| Jiawei Chen
Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province 570311, People’s Republic of China
| Shuai Zhang
Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province 570311, People’s Republic of China
نشانی اینترنتی
https://ijbms.mums.ac.ir/article_23143.html
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Original Article
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